HomeNewsNew biochip could quickly triage people after radiation exposure

New biochip could quickly triage people after radiation exposure

August 21, 2013

A portable device that can measure a person’s radiation exposure in minutes using radiation-induced changes in the concentrations of certain blood proteins. This image shows a magneto-nanosensor chip reader station, chip cartridge, and chip. (Credit: S. Wang)

Berkeley Lab scientists have helped to develop a biochip that could quickly determine whether someone has been exposed to dangerous levels of ionizing radiation.

The first-of-its-kind chip has an array of nanosensors that measure the concentrations of proteins that change after radiation exposure.

Although still under development, the technology could lead to a hand-held device that “lights up” if a person needs medical attention in the aftermath of an incident involving radiation.

Initial tests on mice found that the technology only requires a drop of blood, measures radiation dose in minutes, and yields results for up to seven days after exposure.

The technology was co-developed by scientists from Berkeley Lab and Stanford University, with help from researchers from the Armed Forces Radiobiology Research Institute, UC Davis School of Medicine, and the Methodist Hospital Research Institute’s Center for Biostatistics. The scientists report their research in a paper recently published in the open-access journal Scientific Reports.

How to identify people who require immediate care

“More work is needed, but the chip could lead to a much-needed way to quickly triage people after possible radiation exposure,” says Andy Wyrobek of Berkeley Lab’s Life Sciences Division. He led the multi-institutional team that developed the panel of radiation-sensitive blood proteins. “The goal is to give medical personnel a way to identify people who require immediate care. They also need to identify the expected much larger number of people who receive a dose that doesn’t require medical attention.”.

Currently, the most common way to measure radiation exposure is a blood assay called dicentric chromosome assay, which tracks chromosomal changes after exposure. Another approach is to watch for the onset of physical symptoms. But these methods take several days to provide results, which is far too late to identify people who’d benefit from immediate treatment.

Over the past several years, Wyrobek and colleagues in Berkeley Lab’s Life Sciences Division have explored the biochemical signatures of radiation dose. They’ve identified more than 250 proteins that change after exposure. These proteins can serve as biomarkers that indicate whether a person has been exposed to radiation, and by how much. What’s been lacking is a platform that puts these biomarkers to use.

Meanwhile, in the laboratory of Stanford University’s Shan Wang, researchers have pioneered the use of magnetic nanoparticles and giant magnetoresistive sensors for bio-detection. These sensors are coated with molecules that are designed to capture other “target molecules.” The sensors produce electrical signals when the target molecule, followed by a magnetic nanoparticle, attach to it. In this way, a person can detect the presence of nanoscale objects such as proteins — even though the objects are invisible to the naked eye.

Protein biomarkers + magneto-nanosensors

The two groups began working together a couple of years ago. Wyrobek’s team supplied antibodies for two protein biomarkers of radiation exposure. Wang’s team incorporated these antibodies into magneto-nanosensors. They also created a smaller-than-a-penny-sized chip with 64 of these sensors. A shoebox-sized chip reader connects the chip to an electronic circuit board. The chip reader can be linked to a laptop or smartphone for easy readout.

They tested the system using blood from mice that had been exposed to radiation. Here’s how it works: A drop of blood is placed on the chip. The biomarker proteins in the blood attach themselves to an antibody on one of the chip’s 64 magneto-nanosensors. A second step adds detection antibodies and magnetic nanoparticles to each “captured” protein. The sensors recognize the nanoparticles’ presence, and send electronic signals to the circuit board that indicate the number of proteins present.

Their proof of principle test matched results obtained via a widely used molecule-detection test called an ELISA assay. It also worked up to seven days after exposure.

The scientists next hope to add antibodies for additional proteins to the chip so it can detect the presence of even more biomarkers.

The research was funded primarily by the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority.

Comments (5)

This is essentially the same technology as an ELISA on a chip that requires relatively low sample volumes compared to traditional ELISA (Enzyme Linked Immunosorbent Assay). I guess a more appropriate name would be MLISA, since you’re linking a magnet to the target analyte and detecting the resultant magnetic field instead of using an enzyme-substrate color reaction to detect light absorbance.
Since an antibody can be produced for pretty much any large molecule analyte (greater than about 8 kilodaltons), this technology can be applied to nearly the entire diagnostic field, not just radiation exposure. I’m interested to know which biomarkers they’re targeting here and why the capture antibody would only be specific for the radiated version. It seems that you’d have a lot of specificity issues and would have a hard time with false-positives/negatives as a result. I guess you could help solve the problem by targeting multiple of the 250 analytes simultaneously and calculating probabilities based on those results.

Answered my own question by reading the full journal article. That’s cool that Nature made it open for public reading. It seems that the biomarkers in question, Flt3lg and Saa1 show elevated levels immediately following radiation exposure, and reliably predict dose when they’re measured. Since the assay is based on quantitative measurement of multiple biomarkers that express primarily when exposure to radiation is seen, it accurately indicates whether dosing occurred, as well as the magnitude of the dose. Cool stuff.
I also learned what a spin-valve is, which is a technology that depends on thin-layer bimetal coatings changing their resistance in the presence of magnetic fields. The presence of the magnetically-tagged detection antibody, and its resultant magnetic field, causes the resistance of the bimetal material to change.
In the past I’ve used electrochemiluminescent (ECL) assays where the detection antibody is tagged with a chemical that lights up when a current is passed through the electrolytic reading buffer. This has the benefit of several-fold increased levels of sensitivity over the ELISA detection method. I’d be interested to see a side-by-side comparison of this magnetic detection technology to the sensitivity of the ECL. I would guess that based on their ability to use approximately 40 microliter sample volumes that they get similar levels of sensitivity to ECL or maybe better. Add that to the fact that it’s much quicker than an ECL (which really only differs from ELISA in the method of detection, not how the assay is performed), it would make this a far superior large-molecule detection platform to that which is in wide use today in diagnostic and research labs.
Another disadvantage that I’ve seen with ECL is that the reading process destroys everything inside of the microplate that you’re reading, so multiple reads are impossible. If the reading process fails, the whole experiment needs to be scrapped and started over. In rapid-diagnostic circumstances, this is obviously unacceptable. I wonder if the same is the case for the highlighted method?

It’s an idea that might make you feel uncomfortable if nuclear threats are high. But the fear of radioactivity is related to its invisibility AND to its scarcity. Think of chemicals. OK, your tongue and nose can avoid you a lot of bad things with them, but nature and man have loads of nasty molecules that you would not feel at all (dioxines, …) and whose monitoring in the environement is done only at spots and not everywhere. Conversely, with today electronics, it would be easy (although not desirable for other reasons) to have radioactivity monitoring at every corner or in your own house (radon). Miners extracting the “pechblende” (“cursed ore” as far as I can remember the etimology) would have been cautious in their job with continuous radioactivity monitoring available.

Of course, accepting to live with radioactivity as a “familiar” background threat, much as lightnings, tornadoes, and man-made catastrophes (dam breaking, chemical plant bleaks, smog,…) would not occur in this century but could be part of a technological man’s future without being necessarily associated to nuclear winter. The threats would come, as for chemicals, from concentrated radioactivity as in nuclear plants or, coming back to chemicals, as when tens of tons of chemical known as kerosene and that reacts with oxygen, are ignited when a fuel-loaded airplane strikes a building.

So it all comes from the concentrated / not concentrated scales in this broader perspective